SARTORIUS Weckner 3 Korr Ambr 250 High Throughput Perfusion User Manual

Simplifying Progress
Ambr® 250
High Throughput Perfusion
Fast Track Intensified
Cell Culture Processes

Weckner 3 Korr Ambr 250 High Throughput Perfusion

A Fully-Automated Bioreactor System for Intensified Cell Culture Process Development
Ambr® 250 High Throughout Perfusion is a parallel bioreactor system for rapid development of scalable perfusion processes using 100 – 250 mL single- use bioreactors and a fully automated liquid handling platform. The system supports the typical range of hollow fibre cell retention applications, with up to 24 fully single-use perfusion bioreactors in parallel. This step change in perfusion process development capability dramatically accelerates optimization of intensified cell culture processes leading to lower production volumes and reduced cost of goods.
Productivity
Ambr® 250 dramatically improves laboratory productivity, enabling cell culture scientists to carry out many times more perfusion culture experiments and full DoE experiments at a fraction of the cost compared with traditional perfusion- enabled benchtop bioreactors.
Wide Range of Fed-Batch and Perfusion Culture Conditions
Perfusion cultures can be fully optimized over a wide range of important parameters, including target cell density, crossflow rate, perfusion rate, bleed volume, bleed frequency and filter type, as well as typical culture and bioreactor process conditions such as clone, media, pH, temperature, RPM and gas flows.
The Ambr® 250 High Throughput Perfusion system is also capable of operating in fed-batch mode using standard Ambr® 250 bioreactors.
Scalability
With the industry standard Ambr® 250 High Throughput mammalian cell culture bioreactor at its core, the Ambr® 250 High Throughput Perfusion system can provide highly predictive and scalable performance for fed-batch cultures, and has equivalent potential for perfusion processes.
Convenience
The fully automated liquid handler carries out bioreactor sampling and reagent additions, saving hours of process support time. Fully integrated single-use perfusion bioreactors dramatically reduce setup, cleaning and turnaround time, decreasing cost per experiment and allowing high system utilization with minimal development timelines.

System Features

The Ambr® 250 High Throughput Perfusion System Combines 12 or 24 Bioreactor Stations, Integrated Perfusion Pumps, Bleed and Permeate Collection with a Fully Automated Platform.

1. Automated liquid handler
   The fully automated liquid handler carries out bioreactor sampling and liquid additions, significantly reducing manual operator interactions.

2. Integrated analytics
   The liquid handler transfers samples to a range of optional integrated analyzers, enabling fully automated real-time feedback control loops based on these at-line assays. Optional analyzers: Ambr® Analysis Module; BioProfile FLEX2; Vi-CELL XR; Cedex HiRes.

3. Bioreactor station array
   12 or 24 bioreactor stations in parallel with full individual process control, offers convenient set-up and simplifies running of full DOE experiments.

4. Permeate and bleed flow control and collection system
   The system includes perfusion crossflow and permeate pumps, automated bleed functions, and both permeate and  bleed fluid collection sets with collection bag and tubing management features. Also includes a walk-away permeate sampling system for samples up to 10 mL.

5. Integrated biological safety cabinet
   A class II biological safety cabinet designed to maintain an aseptic environment even during robot manipulation of bioreactors, significantly reducing any risk of process contamination.

6. Perfusion towers
   Perfusion towers support and control key elements of the Ambr® 250 singleuse perfusion bioreactors such as the perfusion pump chambers, pinch valve cassette and perfusion filter.

Bioreactor Vessels

Ambr® 250 High Throughput Single-Use Perfusion Bioreactors Include All Components
Required for Perfusion Culture, Fully Assembled and Irradiated
Single-use perfusion bioreactors significantly reduce staff time needed for set-up and cleaning, and enable rapid system turnaround, increasing system utilization, efficiency and reducing development timelines. Fully assembled and irradiated components further reduce set-up time and minimize risk of lost experiments.
Bioreactor key features
Core features in Ambr® 250 High Throughput Perfusion bioreactors which are also present in standard mammalian cell culture bioreactors include:

• 100-250 mL working volume with baffles
• Dual 26 mm pitched blade impeller
• Spot-based DO sensor
• Disposable pH electrode
• Integrated gas inlet and outlet filters
• Robotic compatible cap for sampling
• Sparger and headspace gassing options
• Integrated exhaust gas condenser

1. Bioreactor perfusion features
   The single-use perfusion bioreactor includes a high efficiency multihole sparger capable of supporting very high cell densities. Two dip tubes allow flow of culture to and from the perfusion pump and filter, plus automated bleeding and bleed-to-level functions.

2. Perfusion pump chambers
   Single-use pump chambers are used to drive the exchange of culture fluid between the bioreactor and the hollow fibre filter. The pump chamber assembly includes retaining clips for the cell retention filter and snaps quickly and neatly into place on the main system perfusion tower.

3. Cell retention filter
   The industry standard approach to cell retention, using a hollow fibre membrane. Options include a 0.2 µm or a 30 kDa filter as standard, and the filter can also be changed by the user before or during the experiment.

4. Pressure sensors
   Single-use pressure sensors connect quickly to the perfusion towers and continuously monitor pressure at the culture fluid inlet and permeate outlet, enabling online monitoring of transmembrane pressure.

5. Pinch valve cassette
   The single-use pinch valve cassette slots into place on the Ambr ® 250 deck at the base of the perfusion tower. Four pinch valves guide the flow of fluids through the perfusion tubing set and enable automated bleeding functions.

Functions

The System Performs Many
Fully Automated Functions
Bioreactor controller

• Three gasses per bioreactor with mass flow sensing of the mixed gas flow:
  – O ₂
  – C O ₂
  – N₂/air

• Four positive displacement liquid pumps per bioreactor for high precision at low flow rates

• When operating with perfusion bioreactors, three pumps are available for reagent addition to the bioreactor and the fourth liquid pump is used to direct permeate flow from the perfusion filter to a collection bag

• For fed-batch operation using standard Ambr® 250 High Throughput bioreactors, all four liquid pumps are available for reagent additions to the bioreactor

• Individual bioreactor temperature control with heating or cooling

• Individual impeller speed control per bioreactor

• Optional exhaust gas monitoring for O₂ and CO₂

• Integrated CIP | SIP protocols for fluid pumps and liquid lines (via optional autoCIP module)

Perfusion tower

• Ergonomic ‘easy connect’ design for rapid installation of single-use perfusion bioreactors including all single-use perfusion components
• Perfusion culture crossflow pumps for each bioreactor provide individual control of perfusion flowrates
• Pinch valve system controls fluid flow between the bioreactor and perfusion filter, and automatically routes bleed fluid to a collection bag
• Online pressure monitoring at perfusion filter inlet and permeate outlet enable monitoring of transmembrane pressure
• Integrated perfusion tower heaters

Applications

Ambr® 250 High Throughput Perfusion is capable of running in either perfusion culture or fed-batch mode, depending on the type of Ambr 250® High Throughput bioreactors installed. The system is able to cover a wide range of applications in biopharma development, including but not limited to perfusion process operations.

• Perfusion process clone selection
• Perfusion media development
• Perfusion process optimization
• Perfusion process characterization
• Perfusion process scale down model development

Scalability

Single-Use from Cell Line and Process Development to Production Scale

• Geometrical similarity of vessel design
• Consistent mixing and gassing strategies
• High performance gas transfer and mixing
• Reliable single-use platforms

BioPAT® Process Insights
Included with the Ambr® 250 High Throughput system is a 1 year license of BioPAT® Process Insights software application.
BioPAT® Process Insights enables predictive scale conversion and low risk process transfer between supported Sartorius bioreactors: Ambr® 15 and 250, Univessel® SU and Glass and Biostat STR® 50-2000 L.
BioPAT® Process Insights is a standalone, on-premise software application. Each license permits up to 10 concurrent users (seats). License includes maintenance, technical support and any available software releases during the active license period. A new license is required after 1 year to continue usage of the software. Please check the technical specification for minimum computer hardware and software specification requirements.

| |
---|---|---
Ambr® 250 High Throughput Perfusion| Biostat® B-DCU with Univessel® Glass
1 – 10 L| Biostat® D-DCU
10 – 200 L

Also scalable to multi-use technologies

| | |
---|---|---|---
Ambr® 250
High Throughput Perfusion| Biostat® B
Univessel® SU 2L| Biostat STR® 50| Biostat STR® 200
| | |
Biostat STR® 500| Biostat STR® 1000| Biostat STR® 2000|

Similar Geometry and Sensors – scaling up from 0.25L to 2000L
Process Development and Characterization
Production

Germany
Sartorius Stedim Biotech GmbH
August-Spindler-Strasse 11
37079 Goettingen
Phone +49 551 308 0| USA
Sartorius Stedim North America Inc.
565 Johnson Avenue
Bohemia, NY 11716
Toll-Free +1 800 368 7178
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** For further contacts, visit www.sartorius.com
** For more information, please visit www.sartorius.com/en/products /fermentation-bioreactors/ambr-multi-parallel-bioreactors/ambr-250-high- throughput-perfusion

Specifications subject to change without notice.
© 2021 Copyright Sartorius Stedim Biotech GmbH,
August-Spindler-Strasse 11, 37079 Goettingen, Germany
Status: 12 | 08 | 2021

References

• Sartorius | Biopharma, Laboratory, Applied & Life Sciences

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